Most tweeted bioRxiv papers, last 7 days

920 results found. For more information, click each entry to expand.

1: Tracking the popularity and outcomes of all bioRxiv preprints
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Posted to bioRxiv 13 Jan 2019

Tracking the popularity and outcomes of all bioRxiv preprints
446 tweets scientific communication and education

Richard J. Abdill, Ran Blekhman

Researchers in the life sciences are posting their work to preprint servers at an unprecedented and increasing rate, sharing papers online before (or instead of) publication in peer-reviewed journals. Though the popularity and practical benefits of preprints are driving policy changes at journals and funding organizations, there is little bibliometric data available to measure trends in their usage. Here, we collected and analyzed data on all 37,648 preprints that were uploaded to bioRxiv.org, the largest biology-focused preprint server, in its first five years. We find that preprints on bioRxiv are being read more than ever before (1.1 million downloads in October 2018 alone) and that the rate of preprints being posted has increased to a recent high of more than 2,100 per month. We also find that two-thirds of bioRxiv preprints posted in 2016 or earlier were later published in peer-reviewed journals, and that the majority of published preprints appeared in a journal less than six months after being posted. We evaluate which journals have published the most preprints, and find that preprints with more downloads are likely to be published in journals with a higher impact factor. Lastly, we developed Rxivist.org, a website for downloading and interacting programmatically with indexed metadata on bioRxiv preprints.

2: Ecological causes of uneven diversification and richness in the mammal tree of life
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Posted to bioRxiv 04 Jan 2019

Ecological causes of uneven diversification and richness in the mammal tree of life
325 tweets evolutionary biology

Nathan Upham, Jacob A Esselstyn, Walter Jetz

The uneven distribution of species in the tree of life is rooted in unequal speciation and extinction among groups. Yet the causes of differential diversification are little known despite their relevance for sustaining biodiversity into the future. Here we investigate rates of species diversification across extant Mammalia, a compelling system that includes our own closest relatives. We develop a new phylogeny of nearly all ~6000 species using a 31-gene supermatrix and fossil node- and tip-dating approaches to establish a robust evolutionary timescale for mammals. Our findings link the causes of uneven modern species richness with ecologically-driven variation in diversification rates, including 24 detected rate shifts. Speciation rates are a stronger predictor of among-clade richness than clade age, countering claims of clock-like speciation in large phylogenies. Surprisingly, rate heterogeneity in recent radiations shows limited association with latitude, despite the well-known richness increase toward the equator. Instead, we find a deeper-time association where clades of high-latitude species have the highest speciation rates, suggesting that species durations are shorter outside than inside the tropics. At shallower timescales (i.e., young clades), diurnality and low vagility are both linked to greater speciation rates and extant richness. High turnover among small-ranged allopatric species may erase the signal of vagility in older clades, while diurnality may adaptively reduce competition and extinction. These findings highlight the underappreciated joint roles of ephemeral (turnover-based) and adaptive (persistence-based) diversification processes, which manifest as speciation gradients in recent and more ancient radiations to explain the evolution of mammal diversity.

3: Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects
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Posted to bioRxiv 28 Dec 2018

Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects
286 tweets bioinformatics

Fedor Galkin, Alexander Aliper, Evgeny Putin, Igor Kuznetsov, Vadim N Gladyshev, Alex Zhavoronkov

The human gut microbiome is a complex ecosystem that both affects and is affected by its host status. Previous analyses of gut microflora revealed associations between specific microbes and host health and disease status, genotype and diet. Here, we developed a method of predicting the biological age of the host based on the microbiological profiles of gut microbiota using a curated dataset of 1,165 healthy individuals (1,663 microbiome samples). Our predictive model, a human microbiome clock, has an architecture of a deep neural network and achieves the accuracy of 3.94 years mean absolute error in cross-validation. The performance of the deep microbiome clock was also evaluated on several additional populations. We further introduce a platform for biological interpretation of individual microbial features used in age models, which relies on permutation feature importance and accumulated local effects. This approach has allowed us to define two lists of 95 intestinal biomarkers of human aging. We further show that this list can be reduced to 39 taxa that convey the most information on their host's aging. Overall, we show that (a) microbiological profiles can be used to predict human age; and (b) microbial features selected by models are age-related.

4: False-positive neuroimaging: Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding
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Posted to bioRxiv 09 Jan 2019

False-positive neuroimaging: Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding
241 tweets neuroscience

YongWook Hong, Yejong Yoo, Tor D. Wager, Choong-Wan Woo

Hypothesis testing and replication in neuroimaging studies both rely heavily on treating gross anatomical regions as unitary entities for inferential purposes, using them as implicit spatial models. However, data collection and analyses are conducted at the voxel level, and this discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in which findings researchers interpret as replications and confirmations of a priori hypotheses. For example, hypothesizing effects on "amygdala activity" does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed; rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we can refer to as "model degrees of freedom." From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report voxel-level evidence for replication at all. Only 14.1% of the papers used exact coordinate-based or a priori pattern-based models. When we compared the peak coordinates between the original and replication studies that reported peak information, 42.9% of their 'replicated' findings had peak coordinates more than 15 mm away, suggesting that these replications entail two maps quite different at the voxel-level. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative and specific spatial models and tests that are defined at the voxel level to assess replications and hypotheses. These include permutation tests on peak distance and using a priori multivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.

5: Enjoy The Violence: Is appreciation for extreme music the result of cognitive control over the threat response system?
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Posted to bioRxiv 02 Jan 2019

Enjoy The Violence: Is appreciation for extreme music the result of cognitive control over the threat response system?
219 tweets neuroscience

Rosalie Ollivier, Louise Goupil, Marco Liuni, Jean-Julien Aucouturier

Traditional neurobiological theories of musical emotions explain well why extreme music such as punk, hardcore or metal, whose vocal and instrumental characteristics share much similarity with acoustic threat signals, should evoke unpleasant feelings for a large proportion of listeners. Why it doesn't for metal music fans, however, remains a theoretical challenge: metal fans may differ from non-fans in how they process acoustic threat signals at the sub-cortical level, showing deactivated or reconditioned responses that differ from controls. Alternatively, it is also possible that appreciation for metal depends on the inhibition by cortical circuits of a normal low-order response to auditory threat. In a series of three experiments, we show here that, at a sensory level, metal fans actually react equally negatively, equally fast and even more accurately to cues of auditory threat in vocal and instrumental contexts than non-fans. Conversely, cognitive load somewhat appears to reduce fans' appreciation of metal to the level reported by non-fans. Taken together, these results are not compatible with the idea that extreme music lovers do so because of a different low-level response to threat, but rather, highlight a critical contribution of higher-order cognition to the aesthetic experience. These results are discussed in the light of recent higher-order theories of emotional consciousness, which we argue should be generalized to the emotional experience of music across musical genres.

6: Highly-accurate long-read sequencing improves variant detection and assembly of a human genome
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Posted to bioRxiv 13 Jan 2019

Highly-accurate long-read sequencing improves variant detection and assembly of a human genome
166 tweets genomics

Aaron M Wenger, Paul Peluso, William J Rowell, Pi-Chuan Chang, Richard J Hall, Gregory T. Concepcion, Jana Ebler, Arkarachai Fungtammasan, Alexey Kolesnikov, Nathan D Olson, Armin Toepfer, Chen-Shan Chin, Michael Alonge, Medhat Mahmoud, Yufeng Qian, Adam M Phillippy, Michael C. Schatz, Gene Myers, Mark A. DePristo, Jue Ruan, Tobias Marschall, Fritz J. Sedlazeck, Justin M Zook, Heng Li, Sergey Koren, Andrew Carroll, David R Rank, Michael W Hunkapiller

The major DNA sequencing technologies in use today produce either highly-accurate short reads or noisy long reads. We developed a protocol based on single-molecule, circular consensus sequencing (CCS) to generate highly-accurate (99.8%) long reads averaging 13.5 kb and applied it to sequence the well-characterized human HG002/NA24385. We optimized existing tools to comprehensively detect variants, achieving precision and recall above 99.91% for SNVs, 95.98% for indels, and 95.99% for structural variants. We estimate that 2,434 discordances are correctable mistakes in the high-quality Genome in a Bottle benchmark. Nearly all (99.64%) variants are phased into haplotypes, which further improves variant detection. De novo assembly produces a highly contiguous and accurate genome with contig N50 above 15 Mb and concordance of 99.998%. CCS reads match short reads for small variant detection, while enabling structural variant detection and de novo assembly at similar contiguity and markedly higher concordance than noisy long reads.

7: Perception of naturally dead conspecifics impairs health and longevity through serotonin signaling in Drosophila
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Posted to bioRxiv 09 Jan 2019

Perception of naturally dead conspecifics impairs health and longevity through serotonin signaling in Drosophila
129 tweets animal behavior and cognition

Tuhin S Chakraborty, Christi M Gendron, Yang Lyu, Allyson S Munneke, Madeline N DeMarco, Zachary W Hoisington, Scott D Pletcher

Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. In humans, psychological trauma is often associated with the recognition of dead individuals, with chronic exposure leading to persistent mental health issues including depression and post-traumatic stress disorder. The mechanisms that link mental and physical health, and the degree to which these are shared across species, remain largely unknown. Here we show that the vinegar fly, Drosophila melanogaster, has the capability to perceive dead conspecifics in its environment and that this perceptive experience induces both short- and long-term effects on health and longevity. Death perception is mediated by visual and olfactory cues, and remarkably, its effects on aging are eliminated by targeted attenuation of serotonin signaling. Our results suggest a complex perceptive ability in Drosophila that reveals deeply conserved mechanistic links between psychological state and aging, the roots of which might be unearthed using invertebrate model systems.

8: Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification
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Posted to bioRxiv 13 Jan 2019

Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification
127 tweets developmental biology

Ricard Argelaguet, Hisham Mohammed, Stephen Clark, Carine Stapel, Christel Krueger, Chantriolnt Andreas Kapourani, Yunlong Xiang, Courtney Hanna, Sebastien Smallwood, Ximena Ibarra Soria, Florian Buettner, Guido Sanguinetti, Felix Krueger, Wei Xie, Peter Rugg-Gunn, Gavin Kelsey, Wendy Dean, Jennifer Nichols, Oliver Stegle, John Marioni, Wolf Reik

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan. Recent studies employing single cell RNA-sequencing have identified major transcriptional changes associated with germ layer specification. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell fate choice remains unresolved, and the coordination between different epigenetic layers is unclear. Here we describe the first single cell triple-omics map of chromatin accessibility, DNA methylation and RNA expression during the exit from pluripotency and the onset of gastrulation in mouse embryos. We find dynamic dependencies between the different molecular layers, with evidence for distinct modes of epigenetic regulation. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of local lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements, driven by loss of methylation in enhancer marks and a concomitant increase of chromatin accessibility. In striking contrast, the epigenetic landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or epigenetically remodelled prior to overt cell fate decisions during gastrulation, providing the molecular logic for a hierarchical emergence of the primary germ layers.

9: Tumor mutational landscape is a record of the pre-malignant state
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Posted to bioRxiv 11 Jan 2019

Tumor mutational landscape is a record of the pre-malignant state
112 tweets genomics

Kirsten Kübler, Rosa Karlić, Nicholas J Haradhvala, Kyungsik Ha, Jaegil Kim, Maja Kuzman, Wei Jiao, Sitanshu Gakkhar, Kent W. Mouw, Lior Z. Braunstein, Olivier Elemento, Andrew V. Biankin, Ilse Rooman, Mendy Miller, Wouter R. Karthaus, Christopher D. Nogiec, Edouard Juvenson, Edward Curry, Mari Mino-Kenudson, Leif W. Ellisen, Robert Brown, Alexander Gusev, Cristian Tomasetti, Martijn P. Lolkema, Neeltje Steeghs, Carla van Herpen, Hong-Gee Kim, Hwajin Lee, Kristian Vlahoviček, Bradley E. Bernstein, Charles L Sawyers, Katherine A Hoadley, Edwin Cuppen, Amnon Koren, Peter F. Arndt, David N. Louis, Lincoln D. Stein, William D. Foulkes, Paz Polak, Gad Getz

Chromatin structure has a major influence on the cell-specific density of somatic mutations along the cancer genome. Here, we present a pan-cancer study in which we searched for the putative cancer cell-of-origin of 2,550 whole genomes, representing 32 cancer types by matching their mutational landscape to the regional patterns of chromatin modifications ascertained in 104 normal tissue types. We found that, in almost all cancer types, the cell-of-origin can be predicted solely from their DNA sequences. Our analysis validated the hypothesis that high-grade serous ovarian cancer originates in the fallopian tube and identified distinct origins of breast cancer subtypes. We also demonstrated that the technique is equally capable of identifying the cell-of-origin for a series of 2,044 metastatic samples from 22 of the tumor types available as primaries. Moreover, cancer drivers, whether inherited or acquired, reside in active chromatin regions in the respective cell-of-origin. Taken together, our findings highlight that many somatic mutations accumulate while the chromatin structure of the cell-of-origin is maintained and that this historical record, captured in the DNA, can be used to identify the often elusive cancer cell-of-origin.

10: Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
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Posted to bioRxiv 08 Feb 2018

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
112 tweets genetics

Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S Fleur W Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Abdel Abdellaoui, Anke R Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A Rietveld, Pascal N Timshel, Stephen P Tino, Maciej Trzaskowski, Ronald de Vlaming, Christian L Zünd, Yanchun Bao, Laura Buzdugan, Ann H Caplin, Chia-Yen Chen, Peter Eibich, Pierre Fontanillas, Juan R Gonzalez, Peter K Joshi, Ville Karhunen, Aaron Kleinman, Remy Z Levin, Christina M Lill, Gerardus A Meddens, Gerard Muntané, Sandra Sanchez-Roige, Frank J van Rooij, Erdogan Taskesen, Yang Wu, Futao Zhang, 23andMe Research Team, eQTLgen Consortium, International Cannabis Consortium, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium, Adam Auton, Jason D. Boardman, David W Clark, Andrew Conlin, Conor C Dolan, Urs Fischbacher, Patrick JF Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A Ikram, Sonia Jain, Robert Karlsson, Ronald C Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suarez, Matthew B McQueen, Klaus M Schmidt, Melissa C Smart, Matthias Sutter, A Roy Thurik, Andre G Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret Boomsma, Tõnu Esko, Ernst Fehr, David A. Hinds, Magnus Johannesson, Meena Kumari, David Laibson, Patrik K.E. Magnusson, Michelle N Meyer, Arcadi Navarro, Abraham A Palmer, Tune H. Pers, Danielle Posthuma, Daniel Schunk, Murray B Stein, Rauli Svento, Henning Tiemeier, Paul RHJ Timmers, Patrick Turley, Robert J Ursano, Gert G Wagner, James F Wilson, Jacob Gratten, James J Lee, David Cesarini, Daniel J Benjamin, Philipp D Koellinger, Jonathan P Beauchamp

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated (|rˆg| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

11: Chloroplasts navigate towards the pathogen interface to counteract infection by the Irish potato famine pathogen
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Posted to bioRxiv 09 Jan 2019

Chloroplasts navigate towards the pathogen interface to counteract infection by the Irish potato famine pathogen
106 tweets plant biology

Alexia Toufexi, Cian Duggan, Pooja Pandey, Zachary Savage, Maria Eugenia Segretin, Lok Him Yuen, David C. A. Gaboriau, Alexandre Y. Leary, Virendrasinh Khandare, Andrew D. Ward, Stanley W. Botchway, Benji C. Bateman, Indranil Pan, Martin Schattat, Imogen A Sparkes, Tolga Osman Bozkurt

Chloroplasts are light harvesting organelles that arose from ancient endosymbiotic cyanobacteria. Upon immune activation, chloroplasts switch off photosynthesis, produce anti-microbial compounds, and develop tubular extensions called stromules. We report that chloroplasts navigate to the pathogen interface to counteract infection by the Irish potato famine pathogen Phytophthora infestans, physically associating with the specialised membrane that engulfs pathogen haustoria. Outer envelope protein, chloroplast unusual positioning1 (CHUP1), anchors chloroplasts to the host-pathogen interface. Stromules are induced during infection in a CHUP1-dependent manner, embracing haustoria and interconnecting chloroplasts, to form dynamic organelle clusters. Infection-triggered reprogramming of chloroplasts relies on surface immune signalling, whereas pathogen effectors subvert these immune pulses. Chloroplast are deployed focally, and coordinate to restrict pathogen entry into plant cells, a process actively countered by parasite effectors.

12: GToTree: a user-friendly workflow for phylogenomics
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Posted to bioRxiv 05 Jan 2019

GToTree: a user-friendly workflow for phylogenomics
99 tweets bioinformatics

Michael D. Lee

Genome-level evolutionary inference (i.e., phylogenomics) is becoming an increasingly essential step in many biologists' work - such as in the characterization of newly recovered genomes, or in leveraging available reference genomes to guide evolutionary questions. Accordingly, there are several tools available for the major steps in a phylogenomics workflow. But for the biologist whose main focus is not bioinformatics, much of the computational work required - such as accessing genomic data on large scales, integrating genomes from different file formats, performing required filtering, stitching different tools together, etc. - can be prohibitive. Here I introduce GToTree, a command-line tool that can take any combination of fasta files, GenBank files, and/or NCBI assembly accessions as input and outputs an alignment file, estimates of genome completeness and redundancy, and a phylogenomic tree based on the specified single-copy gene (SCG) set. While GToTree can work with any custom hidden Markov Models (HMMs), also included are 13 newly generated SCG-set HMMs for different lineages and levels of resolution, built based on searches of ~12,000 bacterial and archaeal high-quality genomes. GToTree aims to give more researchers the capability to make phylogenomic trees.

13: Insights from Bacillus anthracis strains isolated from permafrost in the tundra zone of Russia
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Posted to bioRxiv 03 Dec 2018

Insights from Bacillus anthracis strains isolated from permafrost in the tundra zone of Russia
99 tweets microbiology

Vitalii Timofeev, Irina Bakhteeva, Raisa Mironova, Galina Titareva, Igor Lev, David Christiany, Alexander Borzilov, Alexander Bogun, Gilles Vergnaud

This article describes Bacillus anthracis strains isolated during an outbreak of anthrax on the Yamal Peninsula in the summer of 2016 and independently in Yakutia in 2015. A common feature of these strains is their conservation in permafrost, from which they were extracted either due to the thawing of permafrost (Yamal strains) or as the result of paleontological excavations (Yakut strains). All strains isolated on the Yamal share an identical genotype belonging to lineage B.Br.001/002, pointing to a common source of infection in a territory over 250 km in length. In contrast, during the excavations in Yakutia, three genetically different strains were recovered from a single pit. One strain belongs to B.Br.001/002, as the Yamal strains. Despite the remoteness of Yamal from Yakutia, whole genome sequence analysis showed that the B.Br.001/002 strains are very closely related. The two other strains contribute to two different branches of A.Br.008/011, one of the remarkable polytomies described so far in B. anthracis population. The geographic distribution of the strains belonging to this polytomy is suggesting that this polytomy emerged in the thirteenth century, in combination with the constitution of a unified Mongol empire extending from China to Eastern Europe. We propose an evolutionary model for B. anthracis recent evolution in which the B lineage spread throughout Eurasia and was subsequently replaced by the A lineage except in some geographically isolated areas.

14: Plants emit remotely detectable ultrasounds that can reveal plant stress
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Posted to bioRxiv 28 Dec 2018

Plants emit remotely detectable ultrasounds that can reveal plant stress
93 tweets plant biology

Itzhak Khait, Raz Sharon, Ran Perelman, Arjan Boonman, Yossi Yovel, Lilach Hadany

Plants communicate with their environment in many ways, using colors and shapes and secreting chemicals. Yet, the possibility that plants emit airborne sounds that reveal their condition has not been investigated. Here, we develop a novel method for remotely detecting plant sound emission. We use it to demonstrate, to our knowledge for the first time, that plants emit sounds that can be recorded from a distance. We recorded ~65 dBSPL ultrasonic sounds at 10 cm distance from tomato and tobacco plants, suggesting that these sounds could be detected by many animals from up to several meters. We further train machine learning algorithms to identify the physiological condition of tomato and tobacco plants based solely on the emitted sounds. We successfully classified the plant's condition - dry, cut, or intact - based on its emitted sounds. Our results suggest that animals, and possibly even other plants, could use sounds emitted by plants to gain information about the plant's condition. More investigation on plant bioacoustics in general and on sound emission in plants in particular may open new avenues for understanding plants, and their interactions with the environment.

15: Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval.
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Posted to bioRxiv 08 Jan 2019

Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval.
89 tweets genetics

Emily A King, J Wade Davis, Jacob F Degner

Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. Taking advantage of recent clinical development advances and rapid growth in GWAS datasets, we extend the original work using updated data, test whether genetic evidence predicts future successes and introduce statistical models adjusting for target and indication-level properties. Our work confirms drugs with genetically supported targets were more likely to be successful in Phases II and III. When causal genes are clear (Mendelian traits and GWAS associations linked to coding variants), we find the use of human genetic evidence increases approval from Phase I by greater than two-fold, and, for Mendelian associations, the positive association holds prospectively. Our findings suggest investments into genomics and genetics are likely to be beneficial to companies deploying this strategy.

16: Recording of "sonic attacks" on U.S. diplomats in Cuba spectrally matches the echoing call of a Caribbean cricket
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Posted to bioRxiv 04 Jan 2019

Recording of "sonic attacks" on U.S. diplomats in Cuba spectrally matches the echoing call of a Caribbean cricket
85 tweets biophysics

Alexander L Stubbs, Fernando Montealegre-Z

Beginning in late 2016, diplomats posted to the United States embassy in Cuba began to experience unexplained health problems including ear pain, tinnitus, vertigo, and cognitive difficulties which reportedly began after they heard strange noises in their homes or hotel rooms. In response, the U.S. government dramatically reduced the number of diplomats posted at the U.S. embassy in Havana. U.S. officials initially believed a sonic attack might be responsible for their ailments. The sound linked to these attacks, which has been described as a high-pitched beam of sound, was recorded by U.S. personnel in Cuba and released by the Associated Press (AP). Because these recordings are the only available non-medical evidence of the sonic attacks, much attention has focused on identifying health problems and the origin of the acoustic signal. As shown here, the calling song of the Indies short-tailed cricket (Anurogryllus celerinictus) matches, in nuanced detail, the AP recording in duration, pulse repetition rate, power spectrum, pulse rate stability, and oscillations per pulse. The AP recording also exhibits frequency decay in individual pulses, a distinct acoustic signature of cricket sound production. While the temporal pulse structure in the recording is unlike any natural insect source, when the cricket call is played on a loudspeaker and recorded indoors, the interaction of reflected sound pulses yields a sound virtually indistinguishable from the AP sample. This provides strong evidence that an echoing cricket call, rather than a sonic attack or other technological device, is responsible for the sound in the released recording. Although the causes of the health problems reported by embassy personnel are beyond the scope of this paper, our findings highlight the need for more rigorous research into the source of these ailments, including the potential psychogenic effects, as well as possible physiological explanations unrelated to sonic attacks.

17: Microtubule plus-end dynamics link wound repair to the innate immune response
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Posted to bioRxiv 06 Jan 2019

Microtubule plus-end dynamics link wound repair to the innate immune response
80 tweets cell biology

Clara Taffoni, Shizue Omi, Caroline Huber, Sébastien Mailfert, Mathieu Fallet, Jonathan Ewbank, Nathalie Pujol

As a first line of defence against the environment, the epidermis protect animals from infection and physical damage. In C. elegans, wounding the epidermal epithelium triggers both an immune reaction and a repair response. Exactly how these are controlled, and the degree to which they are inter-connected remains unclear. To address these questions, we established a simple system for simultaneously inflicting precise laser wounds and imaging at high spatial and temporal resolution. We show that in C. elegans, wounding provokes a rapid sealing of the plasma membrane, involving reorganisation of phosphatidylinositol 4,5-bisphosphate domains. This is followed by a radial recruitment at the wound site of EBP-2/EB1, a protein that binds the plus ends of microtubules. EB1 recruitment is accompanied by a reorganisation of microtubules, required for the subsequent recruitment of actin and wound closure. It is also required for the directed trafficking towards the site of injury of the key signaling protein SNF-12. In the absence of SNF-12 recruitment, there is an abrogation of the immune response. Our results suggest that microtubule dynamics coordinate the cytoskeletal changes required for wound repair and the concomitant activation of the innate immune response.

18: Optical clearing of living brains with MAGICAL to extend in vivo imaging
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Posted to bioRxiv 09 Jan 2019

Optical clearing of living brains with MAGICAL to extend in vivo imaging
78 tweets neuroscience

Kouichirou Iijima, Takuto Oshima, Ryosuke Kawakami, Tomomi Nemoto

To understand brain functions, it is important to observe directly how multiple neural circuits are performing in living brains. However, due to tissue opaqueness, observable depth and spatiotemporal resolution are severely degraded in vivo. Here, we propose an optical brain clearing method for in vivo fluorescence microscopy, termed MAGICAL (Magical Additive Glycerol Improves Clear Alive Luminance). MAGICAL enabled two-photon microscopy to capture vivid images with fast speed, at cortical layer V and hippocampal CA1 in vivo. Moreover, MAGICAL promoted conventional confocal microscopy to visualize finer neuronal structures including synaptic boutons and spines in unprecedented deep regions, without intensive illumination leading to phototoxic effects. Fluorescence Emission Spectrum Transmissive Analysis (FESTA) showed that MAGICAL improved in vivo transmittance of shorter wavelength light, which is vulnerable to optical scattering thus unsuited for in vivo microscopy. These results suggest that MAGICAL would transparentize living brains via scattering reduction.

19: Multiplexed electron microscopy by fluorescent barcoding allows screening for ultrastructural phenotype
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Posted to bioRxiv 09 Jan 2019

Multiplexed electron microscopy by fluorescent barcoding allows screening for ultrastructural phenotype
71 tweets cell biology

Yury Bykov, Nir Cohen, Natalia Gabrielli, Hetty E. Manenschijn, Sonja Welsch, Petr Chlanda, Wanda Kukulski, Kiran Raosaheb Patil, Maya Schuldiner, John A.G. Briggs

Genetic screens performed using high-throughput fluorescent microscopes have generated large datasets that have contributed many insights into cell biology. However, such approaches typically cannot tackle questions requiring knowledge of ultrastructure below the resolution limit of fluorescent microscopy. Electron microscopy (EM) is not subject to this resolution limit, generating detailed images of cellular ultrastructure, but requires time consuming preparation of individual samples, limiting its throughput. Here we overcome this obstacle and describe a robust method for screening by high-throughput electron microscopy. Our approach uses combinations of fluorophores as barcodes to mark the genotype of each cell in mixed populations, and correlative light and electron microscopy to read the fluorescent barcode of each cell before it is imaged by electron microscopy. Coupled with an easy-to-use software workflow for correlation, segmentation and computer image analysis, our method allows to extract and analyze multiple cell populations from each EM sample preparation. We demonstrate the method on several organelles with samples that each contain up to 15 different yeast variants. The methodology is not restricted to yeast, can be scaled to higher-throughput, and can be utilized in multiple ways to enable electron microscopy to become a powerful screening methodology.

20: Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
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Posted to bioRxiv 09 Oct 2018

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
71 tweets genetics

David M. Howard, Mark James Adams, Toni-Kim Clarke, Jonathan D. Hafferty, Jude Gibson, Masoud Shirali, Jonathan Coleman, Saskia P Hagenaars, Joey Ward, Eleanor M. Wigmore, Clara Alloza, Xueyi Shen, Miruna C. Barbu, Eileen Y. Xu, Heather C Whalley, Riccardo E Marioni, David J Porteous, Gail Davies, Ian J Deary, Gibran Hemani, Klaus Berger, Henning Teismann, Rajesh Rawal, Volker Arolt, Bernhard T. Baune, Udo Dannlowski, Katharina Domschke, Chao Tian, David A. Hinds, 23andMe Research Team, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Maciej Trzaskowski, Enda M. Byrne, Stephan Ripke, Daniel J Smith, Patrick F Sullivan, Naomi R. Wray, Gerome Breen, Cathryn M Lewis, Andrew M McIntosh

Major depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

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